Autonomously Contracting Human Cardiomyocytes Generated from Adult Pancreatic Stem Cells and Enhanced in Co-Cultures with Myocardial Biopsies

Abstract

Myocardial regeneration with artificially applied cardiomyocytes is emerging as a promising issue of significant scientific and clinical impact. Nevertheless the source of cells for human cardiomyocyte differentiation especially from adult tissue is still unclear. We hypothesized that human pancreatic stem cells may differentiate into cardiomyocyte-like cells and may increase in number when co-cultured with myocardial tissue. Adult stem cells were harvested from pancreatic tissue of patients undergoing operative procedures including the pancreas. The cells were selected, cultured and passaged. To promote self-differentiation into cardiomyocytes, human pancreatic stem cells were co-cultered with biopsies of human myocardium. After co-culture and breeding, cells were phenotyped as well with respect to RNA, protein and cardiomyocyte specificity at the electron-microscopic level. Pancreatic stem cells have already differentiated spontaneously into cardiomyocyte-like cells performing netlike cell clusters with rare but distinct multilocular cellular autonomous contractions with a frequency of about 20 beats per minute. The number of contracting areas however could be enhanced by co-culture with human myocardial biopsies. On RNA and protein levels as well as in electron-microscopy evidence for cardiomyocyte specificity is shown. To the best of our knowledge this is the first report demonstrating the feasibility of generating autonomously contracting cardiomyocyte-like cells from adult human pancreatic stem cells and their enhancement by myocardial co-culture. This procedure might prove to be an alternative source and method for myocardial regenerative medicine.